Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis

Silva, Janine Mayra da; Santos, Tálita Pollyanna Moreira dos; Saraiva, Adriana Machado; Oliveira, Ana Laura Fernandes de; Garlet, Gustavo; Batista, Aline Carvalho; Mesquita, Ricardo Alves; Russo, Remo Castro; Silva, Tarcı́lia Aparecida

doi:10.1016/j.cyto.2018.03.001

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…Immune cell infiltration into local tissue where tumors develop is a key factor in the development and progression of oral cancer, as well as in antitumor activity. Although the immune phenotypes of infiltrating and circulating lymphocytes in OSCC have been extensively studied [6,[22][23][24][25], chemokine expression responsible for immune cell infiltration through the progression of premalignant lesions to OSCC has not been fully elucidated [26][27][28][29]. In the present study, we examined the gene expression of chemokines/ cytokines in the 4NQO-induced OPL and OSCC development.…”

Section: Discussionmentioning

confidence: 94%

Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Yamaguchi

Hiroi

Mori

et al. 2021

Cancers

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Chemokines and cytokines in the tumor microenvironment influence immune cell infiltration and activation. To elucidate their role in immune cell recruitment during oral cancer development, we generated a mouse tongue cancer model using the carcinogen 4-nitroquinoline 1-oxide (4NQO) and investigated the carcinogenetic process and chemokine/cytokine gene expression kinetics in the mouse tongue. C57/BL6 mice were administered 4NQO in drinking water, after which tongues were dissected at 16 and 28 weeks and subjected to analysis using the RT2 Profiler PCR Array, qRT-PCR, and pathologic and immunohistochemical analyses. We found that Th1-associated chemokine/cytokine (Cxcl9, Cxcl10, Ccl5, and Ifng) and Treg-associated chemokine/cytokine (Ccl17, Ccl22, and Il10) mRNA levels were simultaneously increased in premalignant lesions of 4NQO-treated mice at 16 weeks. Additionally, although levels of Gata3, a Th2 marker, were not upregulated, those of Cxcr3, Ccr4, and Foxp3 were upregulated in the tongue tissue. Furthermore, immunohistochemical analysis confirmed the infiltration of CD4+, CD8+, and Foxp3+ cells in the tongue tissue of 4NQO-treated mice, as well as significant correlations between Th1- or Treg-associated chemokine/cytokine mRNA expression and T cell infiltration. These results indicate that CD4+, CD8+, and Foxp3+ cells were simultaneously recruited through the expression of Th1- and Treg-associated chemokines in premalignant lesions of 4NQO-induced mouse tongue tissue.

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Section: Discussionmentioning

confidence: 94%

Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Yamaguchi

Hiroi

Mori

et al. 2021

Cancers

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“…In the combined model, in contrast to simple 4NQO induction, specific gene deletion or overexpression can be studied; compared with simple GEMMs, more specific OSCC can be induced, and genetic changes that are not directly carcinogenic can be investigated. This model can be used to study the role of miRNA (199,200), proteins (82, 184,203), and pathways (201,202) involved in the carcinogenesis of OSCC. Furthermore, the knock-in of green fluorescent protein can be used to label cells with specific gene changes (158,199).…”

Section: Nqo-induced Combined With Gemmsmentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

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Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.

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“…It has been shown that 4-nitroquinoline-1-oxide (4NQO, a chemical carcinogen)-treated ACKR –/– mice develop high levels of IL-1β, IL-6, IL-12, IL-17, TNF-α, CCL2, CCL3, CCL4, CCL5, CCL12, CCR1, CCR2, CCR5, FGF, and VEGF in oral SCC lesions, leading to higher infiltration of Ly6G + neutrophils, mast cells, and F4/80 + macrophages in tumor tissues and proposing an unleashed inflammation in the tumor site. This inflammatory milieu results in the creation of highly proliferative tumor cells ( 61 ). The primary role of macrophages is to protect the body against external infectious pathogens.…”

Section: The Role Of Ackr2 In Diseasesmentioning

confidence: 99%

The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?

et al. 2022

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Chemokines exert crucial roles in inducing immune responses through ligation to their canonical receptors. Besides these receptors, there are other atypical chemokine receptors (ACKR1–4) that can bind to a wide range of chemokines and carry out various functions in the body. ACKR2, due to its ability to bind various CC chemokines, has attracted much attention during the past few years. ACKR2 has been shown to be expressed in different cells, including trophoblasts, myeloid cells, and especially lymphoid endothelial cells. In terms of molecular functions, ACKR2 scavenges various inflammatory chemokines and affects inflammatory microenvironments. In the period of pregnancy and fetal development, ACKR2 plays a pivotal role in maintaining the fetus from inflammatory reactions and inhibiting subsequent abortion. In adults, ACKR2 is thought to be a resolving agent in the body because it scavenges chemokines. This leads to the alleviation of inflammation in different situations, including cardiovascular diseases, autoimmune diseases, neurological disorders, and infections. In cancer, ACKR2 exerts conflicting roles, either tumor-promoting or tumor-suppressing. On the one hand, ACKR2 inhibits the recruitment of tumor-promoting cells and suppresses tumor-promoting inflammation to blockade inflammatory responses that are favorable for tumor growth. In contrast, scavenging chemokines in the tumor microenvironment might lead to disruption in NK cell recruitment to the tumor microenvironment. Other than its involvement in diseases, analyzing the expression of ACKR2 in body fluids and tissues can be used as a biomarker for diseases. In conclusion, this review study has tried to shed more light on the various effects of ACKR2 on different inflammatory conditions.

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Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis

Cited by 8 publications

References 29 publications

Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Simultaneous Expression of Th1- and Treg-Associated Chemokine Genes and CD4+, CD8+, and Foxp3+ Cells in the Premalignant Lesions of 4NQO-Induced Mouse Tongue Tumorigenesis

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?

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